Two epidemiologic studies of young adults from the Detroit metropolitan area and from Zurich, Switzerland, focused on the relationship between migraine and affective disorders, such as major depression, dysthymia, bipolar disorder, and cyclothymia. Through application of current definitions of migraine and psychiatric disorders in structured diagnostic interviews, data have been obtained that strongly support clinical observations on migraine-major depression comorbidity. The findings to support a link between migraine and bipolar disorder are less consistent. Physicians caring for patients with migraine or affective disorders should maintain diagnostic vigilance for comorbid disease and, when present, should consider comorbidity in planning treatment interventions.